Effects of Methylene Blue in Healthy Aging, Mild Cognitive Impairment and Alzheimer's Disease

The subject draws a clock that says 1:45. Performance is rated according to the CLOX directions, and scored as CLOX1 with scores ranging from 0-15 with a lower score indicating greater impairment. CLOX1 reflects performance in a novel and ambiguous situation. The CLOX's second step is a simple copying task. The examiner allows the patient to observe him or her drawing a clock in the circle provided on the scoring sheet. The examiner sets the hands again to 1:45, places the 12, 6, 3, and 9 first, and makes the hands into arrows. The patient is allowed to copy the examiner's clock. This clock is scored as CLOX2 with scores ranging from 0-15 with a lower score indicating greater impairment. Participants can earn up to 15 points for each test, this is summed to give a possible score out of 30 with a higher score indicating less cognitive impairment. Scores reported are from inter-rater reliability

Time frame: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

Population: It was determined after the study began that recruiting middle aged subjects would not be worthwhile.

Functional Magnetic Resonance Imaging (fMRI) measurement of task blocked activation. Measure reflects blood flow counts, and is not a scale with a high or low score.

Time frame: baseline, 2 weeks ± 3 days,12 weeks ± 3 days

Population: There was not sufficient data collected to be analyzed for Mild Alzheimer's disease MB or placebo, only the scale measure was obtained in the next outcome.

fMRI measurement of task blocked activation

Time frame: baseline,2 weeks ± 3 days,12 weeks ± 3 days

Population: There was no data collected to be analyzed for Mild Alzheimer's disease MB or placebo.

fMRI measurement of task blocked activation during Wechsler Memory Scale III

Time frame: baseline, 2 weeks and 12 weeks

Population: There was not sufficient data collected to be analyzed for Mild Alzheimer's disease MB or placebo, only the scale score was measured, as reported in the Wechsler Memory Scale outcome.

Face-Name Task behavioral measures (ie. correct recalls). The FNAME is a cross-modal associative memory test which includes 16 face-name pairs and 16 face-occupation pairs, with a total of 32 pairs to remember. Scores range from 0-32, higher scores are better

Time frame: baseline, 2 weeks ± 3 days,12 weeks ± 3 days

Short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings. The MMSE contains 11 questions with scores ranging from 1-5 depending on how many responses are required for each question. One point is assigned for each correct answer. The total score can range from 0-30 with a higher score indicating better cognitive skills.

Time frame: baseline, 2 weeks ± 3 days,12 weeks ± 3 days

Population: Not all participants returned for all three visits.

Psychomotor vigilance task (PVT) behavioral measures (ie. reaction time). The primary outcome measures of PVT performance, lapses, are defined as reaction times exceeding 500 msec or failure to react. The PVT lapses are believed to represent perceptual, processing, or executive failures in the central nervous system (CNS) Lower scores are better, as they indicate quicker reaction times.

Time frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

The patient is read two stories, out loud, by the test administrator. After each story is read, the patient is then asked to tell the story back to the administrator, as well as possible. Scores range from 0-75, with higher scores indicating better outcome.

Time frame: baseline, then 12 weeks ± 3 days

Population: Not all participants came back for all three visits.

Working memory task behavioral measures (ie. correct number of responses) Score is 0-104, with higher scores being better.

Time frame: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

Resting measurements will be used to assess response and CBF using fMRI. Scores are baseline, percent change between baseline and 2 weeks, baseline and 12 weeks

Time frame: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days

Cerebral blood flow measurements will be acquired during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Cerebral blood flow measurements will be obtained using Arterial Spin Labeling (ASL) during a brief (3-5 minutes) inhalation of medical-grade 5% CO2 in air. Mean regional CBF (rCBF) in gray matter is quantified as ml/100g/min of tissue. The percent change from baseline will be calculated. This will be repeated on weeks 2 and 12.

Time frame: baseline, change from baseline at 2 weeks ± 3 days, change from baseline at 12 weeks ± 3 days

Functional magnetic resonance imaging (fMRI) measurements will be obtained while the subject rests in the scanner, with their eyes closed. The default mode network (DMN) will be identified from the resting state data using temporal concatenation independent components analysis. Dual regression will then be applied to identify the individual subject's DMN maps, followed by the counting of significant voxels above threshold within the DMN masks. This will be repeated on weeks 2 and 12. the voxel is a 3-dimensional unit that embeds the signals in brain scans. As the MRI machine scans through each dimension of the brain millimeter by millimeter, voxels are formed to enclose the signals created by protons-magnet interactions.

Time frame: baseline, 2 weeks ± 3 days, 12 weeks ± 3 days